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Learn more: PMC Disclaimer | PMC Copyright Notice Dermatol Ther (Heidelb) . 2026 Feb 24;16(4):2213–2218. doi: 10.1007/s13555-026-01683-4 Search in PMC Search in PubMed View in NLM Catalog Add to search Minimal Disease Activity as a Therapeutic Goal in Atopic Dermatitis: Predictive Factors of Sustainability in a Multicenter Cohort Francisco Javier Melgosa Ramos Francisco Javier Melgosa Ramos 1 Department of Dermatology, Hospital Universitario Doctor Peset, Av. de Gaspar Aguilar, 90, 46017 Valencia, Spain 2 Department of Dermatology, Hospital Universitario Lluís Alcanyís, Xátiva, Valencia Spain Find articles by Francisco Javier Melgosa Ramos 1, 2, ✉ , Santiago Guillén Climent Santiago Guillén Climent 3 Department of Dermatology, Hospital Universitario Virgen de los Lirios, Alcoy, Spain Find articles by Santiago Guillén Climent 3 , Marta Galarreta Pascual Marta Galarreta Pascual 4 Department of Dermatology, Hospital de Manises, Valencia, Spain Find articles by Marta Galarreta Pascual 4 , Antonio Martorell Antonio Martorell 4 Department of Dermatology, Hospital de Manises, Valencia, Spain Find articles by Antonio Martorell 4 , María Matellanes Palacios María Matellanes Palacios 5 Department of Dermatology, Hospital Arnau de Vilanova, Valencia, Spain Find articles by María Matellanes Palacios 5 , Juncal Roca Ginés Juncal Roca Ginés 6 Department of Dermatology, Hospital General Universitario, Castellón, Valencia Spain Find articles by Juncal Roca Ginés 6 , Javier Sabater Abad Javier Sabater Abad 7 Department of Dermatology, Hospital de la Ribera, Valencia, Spain Find articles by Javier Sabater Abad 7 , Eduardo Bernia Petit Eduardo Bernia Petit 5 Department of Dermatology, Hospital Arnau de Vilanova, Valencia, Spain Find articles by Eduardo Bernia Petit 5 , Víctor González Delgado Víctor González Delgado 8 Department of Dermatology, Hospital Clínico Universitario, Valencia, Spain Find articles by Víctor González Delgado 8 Author information Article notes Copyright and License information 1 Department of Dermatology, Hospital Universitario Doctor Peset, Av. de Gaspar Aguilar, 90, 46017 Valencia, Spain 2 Department of Dermatology, Hospital Universitario Lluís Alcanyís, Xátiva, Valencia Spain 3 Department of Dermatology, Hospital Universitario Virgen de los Lirios, Alcoy, Spain 4 Department of Dermatology, Hospital de Manises, Valencia, Spain 5 Department of Dermatology, Hospital Arnau de Vilanova, Valencia, Spain 6 Department of Dermatology, Hospital General Universitario, Castellón, Valencia Spain 7 Department of Dermatology, Hospital de la Ribera, Valencia, Spain 8 Department of Dermatology, Hospital Clínico Universitario, Valencia, Spain ✉ Corresponding author. Received 2025 Dec 28; Accepted 2026 Feb 3; Collection date 2026 Apr. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13046998 PMID: 41733816 Abstract Introduction Minimal disease activity (MDA) is an emerging therapeutic goal in atopic dermatitis (AD), providing a multidimensional assessment of disease control. Methods We conducted a retrospective multicenter study of adults with moderate-to-severe AD receiving biologics or JAK inhibitors. MDA was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Pruritus Numerical Rating Scale (NRS) ≤ 1. Univariate analyses were performed to identify baseline predictors of sustained MDA at week 52 among patients who had previously achieved MDA at week 16. Results Among 197 patients with week 16 data, 107 (54.3%) achieved MDA. Of these, 59 had data at week 52, and 51 (86.4%) maintained MDA in a per-protocol analysis among patients with available follow-up. Sustained MDA was associated with the absence of hand involvement and fewer prior conventional treatments. No significant differences were found in gender, body mass index (BMI), baseline EASI score, or years of diagnostic delay. A younger age showed a trend toward a significant association with MDA loss. No statistically significant differences were found in the sustainability of MDA at week 52 between treatment groups (dupilumab, tralokinumab, and upadacitinib). Conclusions Sustained MDA among early responders is feasible in real-life AD practice. Baseline characteristics may help identify patients most likely to benefit from early targeted treatment. Keywords: Atopic dermatitis, MDA, Minimal disease activity, Early treatment Key Summary Points Why carry out this study? Minimal disease activity (MDA) is a meaningful and achievable treatment goal for moderate-to-severe atopic dermatitis (AD) in real-world settings. In this multicenter retrospective study, 86.4% of patients who achieved MDA at week 16 maintained it at week 52 in a per-protocol analysis. What was learned from this study? Hand involvement and a higher number of prior conventional systemic treatments were significantly associated with loss of MDA at one year. Younger age showed a non-significant trend toward MDA loss, suggesting potential differences in long-term disease control among patient subgroups. Assessment of MDA at week 16 may help identify patients more likely to maintain disease control at 1 year, supporting its use as a practical clinical milestone in routine care. Open in a new tab Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impairs quality of life [ 1 ]. Recent advances support the adoption of treat-to-target strategies in AD, with minimal disease activity (MDA) emerging as a measurable and clinically relevant therapeutic goal [ 2 – 4 ]. Defined by composite parameters, MDA reflects both physician-assessed and patient-reported outcomes. While trials and registries have begun incorporating MDA, its long-term sustainability and associated predictive factors remain underexplored in real-world clinical settings [ 3 ]. This study aimed to assess the long-term maintenance of MDA in patients receiving biologics or JAK inhibitors for moderate-to-severe atopic dermatitis, and to identify baseline characteristics that may predict sustained therapeutic success. Methods A retrospective, non-interventional multicenter study was conducted at the dermatology departments of four Spanish hospitals from June 2024 to June 2025. It included patients with moderate-to-severe AD treated with biologics (dupilumab and tralokinumab) or JAK inhibitors (upadacitinib, baricitinib, and abrocitinib). Patients treated with lebrikizumab were not included in the analysis because of an insufficient follow-up period, given its recent commercial availability. Patients with available clinical data at week 16 were included. Sustainability analyses at week 52 were performed as a per-protocol analysis among patients who had achieved MDA at week 16 and had available follow-up data at week 52. MDA was defined as Eczema Area and Severity Index (EASI) ≤ 3 and Pruritus Numerical Rating Scale (NRS) ≤ 1. The Eczema Area and Severity Index (EASI) and the Pruritus Numerical Rating Scale (NRS) are validated clinical instruments that do not require permission for use. The primary endpoint was to identify baseline factors (Table 1 ) potentially associated with the sustainability of MDA in patients with moderate-to-severe atopic dermatitis treated with advanced therapies in a real-world setting. The normality of variables was assessed using the Shapiro–Wilk test. A univariate analysis was performed to evaluate the influence of independent variables (age, sex, BMI, years of diagnostic delay, baseline EASI score, involvement of special areas, and number of prior systemic treatments) on the sustainability of MDA at week 52. Quantitative variables were analyzed using Student’s t test or the Mann–Whitney U test, depending on distribution. Categorical variables were compared using chi-square or Fisher’s exact test (as a result of small subgroup sizes and expected cell counts < 5 in some comparisons). Given the limited sample size, no multivariate analysis was conducted. Statistical significance was defined as p < 0.05. Table 1. Comparison of baseline demographic and clinical characteristics between patients who maintained MDA ( N = 51) and those who lost MDA ( N = 8) at week 52 MDA lost ( N = 8) MDA maintained ( N = 51) p value Age, mean (SD) 27.1 (19.1) 41.5 (13.1) 0.086 Sex, % female 60 47.6 0.472 Sex, % male 40 52.4 0.472 BMI, mean (SD) 20.66 (3.5) 22.72 (2.3) 0.146 Diagnostic delay, years, mean (SD) 8.5 (1.2) 8.1 (4.8) 0.617 Prior systemic treatments, mean (SD) 2 (0.5) 0.9 (0.6) < 0.001* Hand involvement, % 80.0 28.6 0.019* Face/neck involvement, % 80.0 57.14 0.6453 Genital involvement, % 0.0 9.52 1.0 Baseline EASI, mean (SD) 20.75 (4.1) 22.68 (7.4) 0.295 Open in a new tab Data are presented as mean (SD) for continuous variables and percentage for categorical variables MDA minimal disease activity, SD standard deviation, BMI body mass index, EASI Eczema Area and Severity Index *Statistically significant ( p < 0.05) The study was conducted in compliance with national regulations and ethical principles governing biomedical research in Spain. According to the national legislation (Law 14/2007 on Biomedical Research and the EU General Data Protection Regulation [GDPR] 2016/679), research involving anonymized data may be exempt from requiring institutional review board (IRB) approval. In this case, owing to the full anonymization of the data, an exemption was granted in accordance with the applicable regulations. The study ensured compliance with all relevant ethical and data protection guidelines. Results A total of 197 patients were included. Among them, 107 (54.3%) patients achieved the MDA target at week 16. Of these, 59 had follow-up data at week 52, and 51 (86.4%) maintained MDA, while 8 (13.6%) lost it (Fig. 1 ). The reduced number of patients with available data at week 52 reflects incomplete follow-up inherent to real-world clinical practice. Fig. 1. Open in a new tab Patient flow diagram showing rates of minimal disease activity (MDA) at week 16 and maintenance status at week 52 Of the 59 patients with available data at week 52, 71.2% received treatment with dupilumab, 20.3% with upadacitinib, and 8.5% with tralokinumab. Table 1 compares the baseline characteristics of patients who maintained MDA at week 52 versus those who lost it. The loss of MDA was significantly associated with hand involvement (80% vs. 28.6%; p = 0.019) and more prior systemic treatments (mean 2.0 vs. 0.9; p < 0.001). No significant differences were observed in BMI, gender, years of diagnostic delay, EASI score at baseline, head/neck or genital involvement. Younger age showed a trend toward a negative impact on the maintenance of MDA ( p = 0.086). No statistically significant differences were found in the sustainability of MDA at week 52 between treatment groups (dupilumab, tralokinumab, and upadacitinib) ( p = 0.098). Although a non-significant trend toward higher maintenance rates was observed in the upadacitinib subgroup, this finding should be interpreted with caution due to the small sample size (Table 2 ). Table 2. Maintenance of minimal disease activity (MDA) at week 52 according to treatment received N = 59 a MDA lost (%) MDA maintained (%) Dupilumab 14.3 85.7 Tralokinumab 40 60 Upadacitinib 0 100 Open in a new tab a Number of patients with available data (who reached the follow-up period) for MDA at week 52 and who had achieved MDA at week 16 Discussion The long-term maintenance of MDA represents a growing challenge in the management of moderate-to-severe AD [ 3 ], particularly as patient and physician expectations increasingly shift toward sustained disease control and symptom relief [ 5 ]. In this context, identifying reliable predictors of therapeutic durability is essential to optimizing clinical decision-making. Our real-world data suggest that early achievement of MDA is not only feasible but may also signal a trajectory toward sustained control at 1 year. Among baseline factors, lower prior systemic treatment exposure was significantly associated with maintenance of MDA at week 52, while older age showed a non-significant trend toward better sustainability. The high proportion of patients maintaining MDA at 1 year suggests that early response may be associated with a more favorable disease trajectory, although this observation should be interpreted descriptively rather than causally. Hand involvement emerged as a significant predictor of MDA loss. This aligns with the recognized immunological complexity of hand eczema, where overlapping inflammatory pathways may limit efficacy of targeted treatments [ 1 ]. Interestingly, this negative prognostic effect was not seen with face/neck or genital involvement possibly as a result of the limited sample size or differing inflammatory profiles. Although no statistically significant differences were observed between treatment groups, a non-significant trend favoring upadacitinib was noted. This observation aligns with the Level-UP trial [ 6 ], and may reflect the broader cytokine inhibition profile of JAK inhibitors compared to biologics. However, interpretation is limited by small subgroup sizes, particularly for tralokinumab. Our results are consistent with prior findings. Rodriguez-Sanna et al. [ 7 ] highlighted older age and fewer prior treatments as favorable predictors of achieving MDA with upadacitinib. Similarly, Melgosa Ramos et al. [ 8 ] identified longer diagnostic delay and higher prior treatment burden as associated with poor short-term outcomes. Ferrucci et al. [ 9 ] also reported that younger age and the presence of comorbid atopic features (such as conjunctivitis or food allergy) were associated with a lower likelihood of achieving MDA with dupilumab. While these findings highlight the potential prognostic role of baseline patient phenotype, available evidence remains heterogeneous, and the impact of comorbid atopic features on treatment response should be interpreted with caution. Collectively, our findings advocate for the integration of MDA as a clinically meaningful and attainable treatment target in daily practice [ 2 , 3 ]. Identifying patients with favorable baseline profiles can support more personalized therapy choices and earlier intervention strategies. Moreover, sustained MDA may represent a step toward long-term disease control and has been proposed as a potential proxy for disease modification, particularly in the context of treatment tapering or discontinuation [ 10 ]. An additional challenge when interpreting these results is the lack of consensus regarding the definition of MDA in atopic dermatitis. Different studies have applied heterogeneous criteria, including IGA-based definitions or EASI75 thresholds, as well as varying patient-reported outcome measures. This methodological heterogeneity limits direct cross-study comparisons and should be taken into account when contextualizing our findings. The main limitations of this study include its retrospective nature, lack of a control group, and relatively small sample size, particularly when stratifying by treatment. In addition, the number of patients with available data at week 52 was limited, reflecting incomplete follow-up inherent to routine clinical practice. Moreover, multivariate analyses could not be conducted because of the limited number of events, restricting the ability to adjust for potential confounders. Consequently, the observed associations should be interpreted with caution and considered exploratory and hypothesis-generating rather than confirmatory. Nevertheless, the multicenter design and inclusion of patients treated with both biologics and JAK inhibitors provide a representative overview of current real-life clinical practice. Conclusions MDA is an achievable and sustainable goal in real-world AD management. Baseline characteristics such as a lower prior systemic treatment burden may help identify patients with better long-term outcomes and guide more personalized treatment strategies. Acknowledgments Medical Writing/Editorial Assistance No medical writing, editorial assistance, or AI-based tools were used in the preparation of this manuscript. Author Contributions Francisco Javier Melgosa Ramos, Santiago Guillén Climent, Marta Galarreta Pascual, Antonio Martorell, María Matellanes Palacios, Juncal Roca Ginés, Javier Sabater Abad, Eduardo Bernia Petit, and Víctor González Delgado equally contributed to the conception and design of the study, data collection, data interpretation, drafting of the manuscript, and critical revision of the content. All authors approved the final version of the manuscript to be published. Funding No funding or sponsorship was received for this study or for the publication of this article. Data Availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Declarations Conflict of Interest Francisco Javier Melgosa Ramos has received honoraria and/or travel grants and/or has acted as an advisory board member for Novartis, AbbVie, Janssen Cilag, UCB, Lilly, LEO Pharma, L’Oréal, Sanofi, Almirall, and Amgen. Antonio Martorell has acted as a consultant, advisory board member, and investigator, and has received honoraria from Novartis, AbbVie, Janssen Cilag, UCB, Lilly, LEO Pharma, L’Oréal, Sanofi, Sandoz, Boehringer Ingelheim, and Amgen. Santiago Guillén Climent, Marta Galarreta Pascual, María Matellanes Palacios, Juncal Roca Ginés, Javier Sabater Abad, Eduardo Bernia Petit, and Víctor González Delgado have nothing to disclose. Ethical Approval The study was conducted in compliance with national regulations and ethical principles governing biomedical research in Spain. According to the national legislation (Law 14/2007 on Biomedical Research and the EU General Data Protection Regulation [GDPR] 2016/679), research involving anonymized data may be exempt from requiring institutional review board (IRB) approval. In this case, owing to the full anonymization of the data, an exemption was granted in accordance with the applicable regulations. The study ensured compliance with all relevant ethical and data protection guidelines. Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Drucker AM, Lam M, Prieto-Merino D, et al. Systemic immunomodulatory treatments for atopic dermatitis: living systematic review and network meta-analysis update. JAMA Dermatol. 2024;160(9):936–44. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. Silverberg JI, Gooderham M, Katoh N, et al. Combining treat-to-target principles and shared decision-making: international expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis. J Eur Acad Dermatol Venereol. 2024;38(11):2139–48. [ DOI ] [ PubMed ] [ Google Scholar ] 3. Gooderham M, Kirchhof MG, Turchin I, Wiseman M, Jain V, Sihota A. The potential value of minimal disease activity in atopic dermatitis. 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A perspective on potential disease modification in atopic dermatitis. Int J Dermatol. 2025;64(8):1337–8. [ DOI ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Data Availability Statement The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. 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